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after moving ~/.PlayOnLinux to my 2nd hard drive:

/media/media/.PlayOnLinux

and adding a symlink to its place:

user:~$ ln -s /media/media/.PlayOnLinux .PlayOnLinux

whenever i run an application or a game im getting this error:

Error in FS_Check
The following file is located on a fuse filesystem.
It might prevent wine from working

something.exe

Can someone help me fix this?

The issue is not with the symlink, but with the filesystem type that's now storing .PlayOnLinux; Not all filesystems implement all features to run Wine, only full POSIX ones (ext*, Reiserfs, XFS, Btrfs,...) are known to work perfectly.
Running programs from others like FUSE-based filesystems may or may not work, depending on the features used by the program. But to avoid this source or errors, PlayOnLinux checks the filesystem type and by default prevent running programs under those conditions.
You can now:
- put things back in place
- format at least a part of your 2nd harddrive with one of the supported filesystems
- disable this check, but then Wine may crash in unexpected ways and we can't give support is can be one of the reasons for failure

The fact is that wineprefix cannot be created in a fuse file system. One of the reason is simple : wineprefixes need symbolic links.

You can disable the check in the case that just a .exe file is not in a valid file system, but you can't install playonlinux root in such a file system.